Enhancement of antibody-dependent cytotoxicity with a chimeric anti-GD2 antibody.
A mouse/human chimeric antibody (ch14.18) was developed that reacts with the disialoganglioside GD2 on the surface of tumor cells of neuroectodermal origin. ch14.18 has the constant regions of a human IgG1 antibody and was expressed in a murine hybridoma. This antibody was produced in tissue culture at concentrations up to 180 mg/liter of spent culture fluid. ch14.18 was characterized and compared to 14.G2a, a murine mAb against GD2 of IgG2a isotype derived from the same parental hybridoma as ch14.18. Scatchard plot analysis of data from saturation binding studies on M21 melanoma cells showed identical binding for ch14.18 and 14.G2a. Indirect immunofluorescence revealed the same staining pattern for ch14.18 and 14.G2a on different melanoma cell lines. Both antibodies were equally capable of targeting M21 xenografts in athymic nude mice. ch14.18- and 14.G2a-activated human C-mediated cytolysis of melanoma cell; however, ch14.18-mediated antibody-dependent cytotoxicity of human effector cells against melanoma cells 50- to 100-fold more efficiently than 14.G2a.
Mueller
B M
BM
Research Institute of Scripps Clinic, La Jolla, CA 92037.
Romerdahl
C A
CA
Gillies
S D
SD
Reisfeld
R A
RA
D000818:Animals; D000911:Antibodies, Monoclonal / Q000235:genetics*; D000920:Antibody-Dependent Cell Cytotoxicity; D002678:Chimera; D004306:Dose-Response Relationship, Immunologic; D005732:Gangliosides / Q000276:immunology*; D006801:Humans; D008546:Melanoma, Experimental / Q000276:immunology*; D051379:Mice; D008819:Mice, Nude; D011994:Recombinant Proteins; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D005732:Gangliosides; D011994:Recombinant Proteins; C019403:ganglioside, GD2